Research Results in Pharmacology最新文献

{"title":"Effects of fumarate on renal vascular reactivity and the modulation of blood pressure in normotensive rats: Possible contribution of the nitric oxide synthase-nitric oxide system","authors":"O. Edosuyi, Myung Choi, I. Igbe, A. Oyekan","doi":"10.3897/rrpharmacology.8.79765","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.79765","url":null,"abstract":"Introduction: Fumarate, the tricarboxylic acid (TCA) cycle intermediary, has been linked to nitric oxide (NO) production. NO plays a prominent role in the physiological regulation of blood pressure and renal hemodynamics. This study is aimed to investigate any contribution of fumarate to blood pressure and renal hemodynamics in normotensive rats with a possible link to the nitrergic system.\u0000 Materials and methods: Fumarate (1, 3 and 10 µmol) was injected into isolated perfused kidneys, pre-constricted with epinephrine (30 µM). The fumarase inhibitor, pyromellitic acid (PMA) (1, 3 and 10 µM), was used to perfuse the isolated kidney and perfusate was collected for nitric oxide and fumarate assays. An acute blood pressure study involved the injection of bolus doses of fumarate (0.1, 0.3 and 1 µg/kg, iv) or PMA (1, 3 and 10 µg/kg, iv) to normotensive rats in the presence of N(ω)-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg, iv) or PMA (1, 3 and 10 µg/kg).\u0000 Results and discussion: Fumarate reduced perfusion pressure and elicited a peak reduction at the highest dose. Perfusing the kidney with PMA caused a paradoxical increase in perfusion pressure (70%, p<0.05), compared to baseline. Bolus doses of fumarate reduced blood pressure (-29.3±6.2 mmHg, p<0.05), cortical blood flow (CBF) and increased medullary blood flow (MBF). L-NAME did not abolish the vasodilatory effect of fumarate, but reduced the magnitude of response (50%, p<0.05). PMA did not significantly affect the vasodilatory effect of fumarate (p>0.05).\u0000 Conclusion: These data suggest that fumarate exerts a vasodilatory effect on renal and systemic hemodynamics that may partly involve the nitric oxide signaling.\u0000 Graphical abstract:\u0000 \u0000 \u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42172278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient receptor potential Ankyrin 1: structure, function and ligands","authors":"N. Pyatigorskaya, O. Filippova, N. S. Nikolenko, A. D. Kravchenko","doi":"10.3897/rrpharmacology.8.90214","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.90214","url":null,"abstract":"Introduction: Transient receptor potential ankyrin 1 (TRPA1) is a protein expressed in many living organisms. During the study of TRPA1, its unique biological role as a universal and polymodal sensor of various altering agents was found. The aim of this study is to search and generalize information about structural features and molecular determinants, mechanisms of activation, action and modulation of TRPA1 as a universal pain and inflammation sensor, as well as the nature of activators and antagonists of this target and their therapeutic potential.\u0000 Materials and methods: This article presents an overview of the results of scientific research of TRPA1, its modulators, as well as an overview of their pharmacological potential over the period from the discovery of these channels to the present, with an emphasis on the last decade.\u0000 Results and discussion: The main collected data on expression, structural features and molecular determinants, mechanisms of activation and action of TRPA1 indicate its role as a universal and labile element of the primary response of the body to adverse exogenous and endogenous factors. Regardless of the nature of the stimulus, hyperstimulation of TRPA1 channels can lead to such phenomena as pain, inflammation, itching, edema and other manifestations of alteration, and therefore TRPA1 blockade can be used in the treatment of various diseases accompanied by these pathological conditions. Currently, TRPA1 antagonists are being actively searched for and studied, as evidenced by a high patent activity over the past 14 years; however, the molecular mechanisms of action and pharmacological properties of TRPA1 blockers remain understudied.\u0000 Conclusion: Acquire of new information about TRPA1 will help in the development of its modulators, which can become promising analgesics, anti-inflammatory drugs, bronchodilators, and agents for the treatment of cardiovascular diseases of new generations.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42674449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of the effect of acetylsalicylic acid and a selective arginase II inhibitor KUD 975 on the correction of hemostatic disorders in experimental preeclampsia","authors":"A. V. Gureeva, O. Severinova, V. Gureev, I. S. Kochkarova, E. V. Avdeyeva","doi":"10.3897/rrpharmacology.8.87539","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.87539","url":null,"abstract":"Introduction: The disruption of the functional state of the vascular endothelium is among the main causes of preeclampsia, which is one of the most common causes of maternal and perinatal mortality. It can be enhanced by the humoral factors secreted by the activated platelets. The use of acetylsalicylic acid is an effective way to prevent preeclampsia. However, its ability to activate eNOS is a prerequisite for researching its ability to correct the disorders in developing preeclampsia, including by reducing the platelet activity. In this case its effect can be enhanced through increasing the bioavailability of L-arginine by using a selective arginase II inhibitor KUD 975. These facts were the prerequisite for conducting this study.\u0000 Materials and methods: The study was conducted on 180 female Wistar rats weighing 250–300 g. Acetylsalicylic acid was used at a dose of 7 mg/kg/day and 10 mg/kg/day, KUD 975 – at a dose of 1 mg/kg/day and 3 mg/kg/day. Adenosine diphosphate (ADP, 6.5 microns), arachidonic acid (ASPI, 0.5 mM), and collagen (3.2 mcg/ml) were used as aggregation inducers.\u0000 Results and discussion: ADMA-like preeclampsia simulation led to an increase in platelet aggregation ability when using all aggregation inducers. This is evidenced by an increase in a degree, rate of aggregation, and a shortened time of thrombus formation. The use of acetylsalicylic acid and a selective arginase II inhibitor KUD 975 led to a decrease in the aggregation ability of platelets and an increase in thrombosis time, while the combined administration of the studied agents showed a more pronounced effect.\u0000 Conclusion: The data obtained while performing a series of experiments strongly indicate a promising outlook for using acetylsalicylic acid and a selective arginase II inhibitor KUD 975 in order to correct emerging disorders in preeclampsia.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48293344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of monoaminergic system in the antidepressant effect of 3-substituted thietane-1,1-dioxide derivative","authors":"I. Nikitina, G. G. Gaisina","doi":"10.3897/rrpharmacology.8.81007","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.81007","url":null,"abstract":"Introduction: The aim of the study was to assess the involvement of the monoaminergic system in the antidepressant effect of a new 3-substituted thietane-1,1-dioxide derivative (N-199/1) using tests with several pharmacological antagonists and agonists.\u0000 Materials and methods: We conducted 3 sets of experiments in white outbred male mice. In Experiment 1, we assessed the antidepressant effect of N-199/1 in the forced swimming test (FST) and tail suspension test (TST) when administered repeatedly for 2 weeks intraperitoneally (i.p.). In Experiment 2, we evaluated the antidepressant effect of N-199/1 in FST and TST when co-administered with 5HT1A- (WAY100635, 0.1 mg/kg), 5HT2A/2C- (ketanserin, 5 mg/kg), 5HT3- (ondansetron, 1 mg/kg) serotonergic and α2-adrenergic (yohimbine, 1 mg/kg) receptors antagonists. In Experiment 3, we assessed the effect of N-199/1 on the hypothermia induced by i.p. injection of α2-adrenergic receptors agonist clonidine (0.3 mg/kg).\u0000 Results and discussion: N-199/1 reduced immobility time (IT) and index of depression (ID) in FST, and did not affect IT in TST, either when administered repeatedly in Experiment 1, or acutely in Experiment 2. In Experiment 2, ketanserin enhanced the effect of N-199/1, decreasing ID by 36%, while WAY100635 and yohimbine antagonized it, increasing ID by 27% and IT by 115%, respectively, in comparison with N-199/1. N-199/1 attenuated the effect of ondansetron, increasing IT by 36%. In Experiment, 3 N-199/1 reduced clonidine-induced hypothermia 1 h after the injection of clonidine. N-199/1 exhibited pronounced antidepressant properties in FST, an agonism to 5HT1A-receptors and an antagonism to 5HT2A/2C- and α2-receptors in tests of neuropharmacological interaction, which indicates an atypical mechanism of its antidepressant action.\u0000 Conclusion: The antidepressant effect of N-199/1 is due to the stimulation of 5HT1A-receptors and blockade of 5HT2A/2C- and α2-receptors.\u0000 Graphical abstract:","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43149545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined anti-mediator therapy for severe destructive forms of acute necrotizing pancreatitis in rats","authors":"T. Firsova, S. A. Alekhin, D. P. Nazarenko, L. Danilenko, Antonina G. Chub, E. Malyutina, T. Lazareva, L. V. Druzhikin","doi":"10.3897/rrpharmacology.8.79939","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.79939","url":null,"abstract":"Introduction: Inflammatory mediators play a major role in pathogenesis of acute pancreatitis with TNF (tumor necrosis factor) as the most important one. Development of effective combined therapy could help to decrease tissue damage, improve results and, finally, diminish the mortality rate in this severe pathology.\u0000 Materials and methods: All the studies were performed on 120 female white Wistar rats, weighing 250±25g. Acute pancreatitis reproduced by an intracanalicular injection of bile salts compound.\u0000 Results and discussion: The data obtained in the course of the study on the pronounced pancreatoprotective effect of infliximab are explained by its key role in the onset of the systemic inflammatory response, and, therefore, with the blockade of tumor necrosis factor alpha in the early stages, there is no pronounced secondary damage to the pancreas, which is reflected in a significant decrease in edema from 4.87±0.03 in the model up to 2.75±0.04, and as a consequence, an improvement in the blood supply of the acinar tissue from 182.38±15.92 PU up to 287.92±14.64 PU, which is expressed in a decrease in the zones of necrosis and in a decrease in mortality and, finally, efficiency coefficient from 13480.000 to 4283.348. A selective blocker of cysteinyl leukotrienes has a less pronounced protective reaction against damage to pancreatocytes, but to a much greater extent than octreotide. That is expressed by changes in the efficiency coefficient to the level of 8621.18 in montelukast group and 12767.30 in octreotide group, respectively. On the other hand, the effect of the use of infliximab does not surpass that of montelukast, and their combined use has a pronounced additive effect, which is proved by the efficiency coefficient at the level of 2390.33. This reaction is explained by the fact that TNF alpha-mediated pathway of activation of leukotriene biosynthesis is the main, but not the only one.\u0000 Conclusion: The combined anti-mediator therapy provides a great opportunity to improve the standard therapy of acute pancreatitis.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47984007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current view on the problem of treating fibrocystic breast disease in terms of herbal medicine","authors":"O. P. Sokolik, G. Prozorova","doi":"10.3897/rrpharmacology.8.79286","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.79286","url":null,"abstract":"Introduction: Fibrocystic breast disease, commonly called fibrocystic breasts or fibrocystic change, is a benign (noncancerous) condition, which is the most common pathology in women of reproductive age. Treatment of fibrocystic breast disease and concomitant pathologies can involve using herbs.\u0000 Materials and Methods: To make an analysis of literary sources on the development of fibrocystic breast disease in the pathogenesis of diseases of the female reproductive system (clinical human (75%) and animal studies (25%)) were published in the period of 2017–2021.\u0000 Results and discussion: The diversity of plants in the world is a promising ground for therapeutic improvisation, allowing for an individual approach to each patient, but, most importantly, creates possibilities for maneuvering in the event of ineffectiveness of any means. In some situations, herbal medicine is not only possible or permissible, but strictly mandatory, and is essentially the only effective therapeutic method, which is relatively safe provided the correct selection of combinations and control by a doctor who applies a certain method of phytotherapy, especially given a duration of treatment. The need for a deeper study is long overdue for the pharmacological capabilities of various plant raw materials in the treatment of not only this pathology, but others as well.\u0000 Conclusion: The development of phytotherapy should be based primarily on scientific developments, but this area can not be considered the prerogative of only phytotherapists, as herbal medicines should be in the arsenal of doctors of all specialties.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46884048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Searching for novel antagonists of adenosine A1 receptors among azolo[1,5-a]pyrimidine nitro derivatives","authors":"D. Yakovlev, P. Vassiliev, Ya. V. Agatsarskaya, A. A. Brigadirova, K. T. Sultanova, M. Skripka, A. Spasov, K. Savateev, V. Rusinov, D. Maltsev","doi":"10.3897/rrpharmacology.8.77854","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.77854","url":null,"abstract":"Introduction: Ligands of adenosine A1Rs are potential candidates for the development of drugs for the treatment of paroxysmal supraventricular tachycardia, angina pectoris, hypertriglyceridemia, type 2 diabetes mellitus, neuropathic pain, and heart failure. At the same time, there is a deficiency of drugs that can regulate the functions of A1 receptors. A number of A1-antagonists are at the various stages of clinical trials; other drugs are not very selective or are characterized by an insufficient breadth of their therapeutic action. Therefore, the search for new medicinal compounds for the prevention and treatment of A1-depended diseases among nitro derivatives of tetrazolo[1,5-a]pyrimidine and 1,2,4-triazolo[1,5-a]pyrimidine is of scientific interest.\u0000 Materials and methods: The search for active compounds was carried out by in silico and in vitro methods. At the first stage, a computer forecast of A1-antagonistic activity was carried out using the Microcosm BioS software. At the second stage, the prediction results were verified in vitro in a model of isolated mouse atria.\u0000 Results and discussion: Based on the results of the prediction by the method of maximum similarity to standards, the most active compounds III, VIII, and XVII were selected. After testing the prediction results by the isolated atria method, the compound VIII was characterized by A1-blocking effect in vitro at a concentration of 10 μmol/L.\u0000 Conclusion: The most promising compound with A1-blocking effect in vitro was identified; it is a derivative of tetrazolo[1,5-a]pyrimidine under the code of VIII. It is of interest for us for further in-depth study of its pharmacological properties.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43706652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically modified animal models of hereditary diseases for testing of gene-directed therapy","authors":"A. Polikarpova, T. Egorova, M. Bardina","doi":"10.3897/rrpharmacology.8.82618","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.82618","url":null,"abstract":"Disease-causing genes have been identified for many severe muscular and neurological genetic disorders. Advances in the gene therapy field offer promising solutions for drug development to treat these life-threatening conditions. Depending on how the mutation affects the function of the gene product, different gene therapy approaches may be beneficial. Gene replacement therapy is appropriate for diseases caused by mutations that result in the deficiency of the functional protein. Gene suppression strategy is suggested for disorders caused by the toxic product of the mutant gene. Splicing modulators, genome editing, and base editing techniques can be applied to disorders with different types of underlying mutations. Testing potential drugs in animal models of human diseases is an indispensable step of development. Given the specific gene therapy approach, appropriate animal models can be generated using a variety of technologies ranging from transgenesis to precise genome editing. In this review, we discuss technologies used to generate small and large animal models of the most common muscular and neurological genetic disorders. We specifically focus on animal models that were used to test gene therapies based on adeno-associated vectors and antisense nucleotides.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48776755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote ischemic preconditioning combined with atorvastatin improves memory after global cerebral ischemia-reperfusion in male rats","authors":"A. Hedayatpour, M. Shiasi, Peyman Modarresi, Alieh Bashghareh","doi":"10.3897/rrpharmacology.8.75753","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.75753","url":null,"abstract":"Introduction: Damage to hippocampus can occur through ischemia. Memory problems are among the most significant disabilities after stroke. Therefore, improving memory is of great interest in helping post-stroke patients. This study demonstrated that intraperitoneally injection of atorvastatin with a short cycle of ischemia-reperfusion in the left femoral artery improved hippocampal CA1 neurons injury and memory problems after global cerebral ischemia.\u0000 Materials and methods: In this article survey, we used 64 animals. Rats were divided into 8 groups, (n=8). Group 1: control; group 2: sham; group 3: global cerebral ischemia (GCI) only; group 4: remote ischemic preconditioning (RIP) + GCI; group 5: GCI + atorvastatin (ATO); group 6: GCI + vehicle; group 7: RIP + GCI + ATO; group 8: RIP + GCI + vehicle. We created global cerebral ischemia (GCI) with 20 min occlusion of the Common carotid artery.\u0000 Results and discussion: Remote ischemic preconditioning could improve rats performance in water maze tests along with a decrease in neuronal death. Also, atorvastatin combined with remote ischemic preconditioning was more effective for memory improvement and reduction of neuronal death. Inconsistent with our result, the function of the animals in the ischemia group was impaired. CA1 hippocampal neurons have an important role in memory and learning, and they can be damaged after cerebral ischemia. Therefore, ischemia can create memory problems. Remote ischemic preconditioning and atorvastatin had a neuroprotective effect and could improve rat performance in water maze test.\u0000 Conclusion: This study showed that remote ischemic preconditioning with atorvastatin could improve CA1 neuronal injury and memory.\u0000 Graphical abstract:\u0000 \u0000 \u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45207417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative activity of a new derivative from the class of N-glycoside of indolo[2,3-a]pyrrolo[3,4-c]carbazoles","authors":"Marina P. Kiseleva, L. Borisova, G. Smirnova, Yu. A. Borisova, A. Lantsova, E. Sanarova, L. Nikolaeva, Lydia V. Ektova, M. V. Komarova","doi":"10.3897/rrpharmacology.8.79424","DOIUrl":"https://doi.org/10.3897/rrpharmacology.8.79424","url":null,"abstract":"Introduction: The creation of highly effective original anticancer drugs remains an urgent direction of scientific research in tumor therapy. One of the promising groups in this regard is indolocarbazoles and their derivatives, which are capable of initiating various pathways of tumor cell death. The aim of the study was to evaluate an antiproliferative activity of a new, Russian derivative of N-glycoside substituted indolocarbazole 6-amino-12-(α-L-arabinopyranosyl)indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione (LCS-1208) on models of transplantable tumors of mice and on human tumors in Balb/c nude mice.\u0000 Materials and methods: Indolocarbazole sensitivity to LCS-1208 was assessed on transplantable tumors of mice – lymphatic leukemia L-1210, cervical carcinoma (CC-5), and colon adenocarcinoma (CAC) by five-fold intraperitoneal administration (ip) of the LCS-1208 substance in single doses of 50, 75, 100 mg/kg. Investigation into the effectiveness of the LCS-1208 lyo dosage form was performed on subcutaneous xenografts of human colon cancer SW620 by an intravenous administration (iv). The antitumor effect was evaluated by the tumor growth inhibition (TGI) and an increase in life span (ILS) of the treated animals as compared with the control ones. Evaluation of specific antitumor activity on xenografts was performed according to the tumor/control (T/C%) criterion (maximum criterion T/C≤42%).\u0000 Results and discussion: According to the results of the study, the most sensitive to the action of the LCS-1208 substance in the case of an ip administration of a total dose of 375 mg/kg were CAC with TGI=97–62%, p≤0.001 up to 16 days after the treatment, and ILS=36% (criteria for TGI≥70% and ILS≥25%). On xenografts of a human colon cancer SW620, the effectiveness of the LCS-1208 lyo drug dosage form within the range of total doses from 50 to 150 mg/kg in case of iv to Balb/c nude mice was set at T/C = 35–2% (criterion T/C<42%).\u0000 Conclusion: The presented results suggest possible effectiveness of LCS-1208 in treatment of colon malignant tumors of humans.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42475977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}